Anthropometric factors, physical activity, and risk of non-Hodgkin's lymphoma in the Women's Health Initiative

Background: Incidence rates of non-Hodgkin's lymphoma (NHL) increased substantially in the United States and worldwide during the latter part of the 20th century, but little is known about its etiology. Obesity is associated with impaired immune function through which it may influence the risk of NHL; other factors reflecting energy homeostasis (height, abdominal adiposity, and physical activity) may also be involved. Methods: We examined the association of anthropometric factors and physical activity with risk of NHL and its major subtypes in a large cohort of women aged 50–79 years old who were enrolled at 40 clinical centers in the United States between 1993 and 1998. Over a mean follow-up period of 11 years, 1123 cases of NHL were identified among 158,975 women. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Height at baseline was positively associated with risk of all NHL and with that of diffuse large B-cell lymphoma (HRs_q4vs.q1 1.19, 95% CI 1.00–1.43 and 1.43, 95% CI 1.01–2.03, respectively). Measures of obesity and abdominal adiposity at baseline were not associated with risk. Hazard ratios for NHL were increased for women in the highest quartile of weight and body mass index at age 18 (HRs_q4vs.q1 1.29, 95% CI 1.01–1.65 and 1.27, 95% CI 1.01–1.59, respectively). Some measures of recreational physical activity were modestly associated with increased risk of NHL overall, but there were no clear associations with specific subtypes. Conclusion: Our findings regarding anthropometric measures are consistent with those of several previous reports, suggesting that early life influences on growth and immune function may influence the risk of NHL later in life.     

FNAC of malignant lymphoma in an area with a high incidence of T-cell lymphoma. Correlation of accuracy of cytologic diagnosis with histologic subtype and immunophenotype

OBJECTIVE: To analyze the usefulness of fine needle aspiration cytology on malignant lymphoma in an area with a high incidence of T-cell lymphoma and to correlate the accuracy of cytologic diagnosis with histologic subtype and immunophenotype. STUDY DESIGN: We retrospectively studied the usefulness of fine needle aspiration cytology in the diagnosis of 49 cases of nodal and extranodal non-Hodgkin's lymphoma (NHL) and seven cases of Hodgkin's disease in a total of 56 patients in whom subsequent excisional biopsy revealed lymphoid malignancy. Slides showing the results of cytologic investigation were reviewed together with the information on which histologic diagnosis was based. On the basis of pathologic variables, such as prognostic groups based on the Working Formulation, so-called grade, cell size based on the modified Rappaport classification, and--in cases of NHL--immunophenotype, the accuracy of original and reviewed cytologic diagnoses was compared. RESULTS: Of the 49 cases of NHL, 8 (16.3%) were inadequate for cytologic diagnosis, and malignant lymphoma was diagnosed or suspected in 36 (73.5%), excluding inadequate specimens; the diagnostic accuracy for NHL was 87.8%. In high grade cases, malignant lymphoma was more easily diagnosed or suspected than in those that were low or intermediate grade. The rate of inadequate cases was highest in the "mixed small and large cell" category, and cases that were "false negative" were either composed entirely of small cells or contained a small cell component. Cytologic diagnosis or suspicion of malignant lymphoma was easily obtained in the "large cell" category, followed by mixed small and large cell and "small cell." Aspirates from non-B-cell type were more frequently acellular than those of B-cell type; with regard to diagnostic accuracy, however, there was no noticeable difference between the two immunophenotypes. CONCLUSION: In many cases in the mixed small and large cell category or where the immunophenotype was non-B, the aspirate was inadequate, and no definitive diagnosis was possible. Many of our cases of T-cell lymphoma were mixed small and large cell, and in Korea, where the incidence of extranodal and T-cell lymphoma is high, the usefulness of FNAC for the initial diagnosis of malignant lymphoma is limited. For a definitive diagnosis, biopsy is required.     

Expected long-term survival of older patients diagnosed with non-Hodgkin lymphoma in 2008-2012

Background: New therapeutic options have led to substantial increases in survival expectations of patients with non-Hodgkin lymphoma (NHL) in recent years. In contrast to many malignancies, survival in older patients has improved in NHL at a rate similar to that in younger patients. In the past, the impact of innovations on long-term survival of NHL patients on the population level has been disclosed only with substantial delay. Methods: We employ a novel model-based projection method to estimate survival expectations of NHL patients age 60+ diagnosed in 2008–2012. Preliminary empirical evaluation of the method using historical data indicates excellent performance in projection of age specific and overall 5- and 10-year relative survival. Results: Overall 5- and 10-year survival projections for 2008–2012 were 67.5% and 56.9%, respectively, 8.2 percentage units (% units) and 15.2% units, respectively, higher than the most recent survival estimates available from traditional cohort analysis. Projected survival decreased with age, ranging from 79.1% for patients age 60–64 to 54.3% for patients age 80+. Projected survival estimates for diffuse large B-cell lymphoma and follicular lymphoma were 59% and 84.9%, respectively. Survival estimates by model-based projection were substantially higher than available cohort estimates for all age groups including 80+, each specific morphology examined, nodal and extranodal disease, and both genders. Conclusions: Patients over 60 diagnosed with NHL in 2008–2012 have much higher long-term survival expectations than suggested by previously available survival statistics.     

Leukocyte-common antigen and vimentin are reliable adjuncts in the diagnosis of non-Hodgkin's lymphoma in fine needle aspirates

Alcohol-fixed fine needle aspirates of 82 non-Hodgkin's malignant lymphomas (NHLs) were tested for the presence of vimentin and leukocyte-common antigen (LCA) by means of monoclonal antibodies (MAbs) and indirect immunofluorescence. All NHLs stained positively for vimentin; the staining was strong in all except three cases. Of the 69 NHLs tested for LCA, 1 (a large cell T-cell lymphoma) was negative while the staining was weak in 6. Thus, vimentin and LCA MAbs are sensitive, specific and reliable complementary diagnostic adjuncts that are useful in the definitive diagnosis of NHLs in alcohol-fixed fine needle aspirates. Their presence in the aspirate confirmed a cytologic diagnosis of NHL in 47 cases, helped to diagnose NHL in 31 cases in which a cytologic differential diagnosis with small cell anaplastic carcinoma could not be made with confidence and helped to change the initial cytologic diagnosis of anaplastic carcinoma to NHL in 4 cases.     

Rate of Primary Refractory Disease in B and T-Cell Non-Hodgkin’s Lymphoma: Correlation with Long-Term Survival

Background

Primary refractory disease is a main challenge in the management of non-Hodgkin’s Lymphoma (NHL). This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients.

Methods

Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%), intensive therapy with autograft (16.9%), or other therapies (19.9%). Among B-cell NHL, 1,356 (47.8%) received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months.

Results

Overall, 690 (22.2%) patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001). Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001). Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001).

Conclusion

Chemosensitivity to primary treatment is crucial for the long-term survival in NHL. This supports the necessity of studies aimed to early identify refractory disease and to develop different treatment strategies for responsive and refractory patients.     

The Epidemiology of Thyroid Cancer in Los Angeles County

More than 300 new cases of thyroid cancer are diagnosed in Los Angeles County every year. The age-adjusted annual incidence rates of this disease for all races combined are 2.4 for males and 6.1 for females. Rates for women are more than twice rates for men in each major ethnic group. Blacks of both sexes have the lowest rates; Japanese, Chinese, other Asians and Spanish-surnamed whites all have rates that are as high as or higher than rates among non-Spanish-surnamed whites. Other demographic patterns include the excess of thyroid cancer among Jewish residents of Los Angeles.There have been an increase in thyroid cancer incidence and a decline in mortality for this disease in the United States over the past several decades. Several possible explanations can be made for these trends. Also, the risk factors for thyroid cancer deserve review.     

Polymorphisms in the nucleotide excision repair gene ERCC2/XPD and risk of non-Hodgkin lymphoma

Non-Hodgkin lymphoma (NHL) represents a complex group of B- and T-cell malignancies characterised by chromosomal translocations. Since defects in DNA repair result in an increased frequency of chromosomal aberrations it has been hypothesised that genetic variation in DNA repair may be associated with risk of NHL. To investigate the relationship between DNA repair and NHL we analysed polymorphisms in XPD (R156R, D312N, K751Q) using DNA collected in a UK population-based case-control study of lymphoma. We observed no association between genetic variation in XPD and risk of NHL. However, the XPD 751 Gln allele was associated with a two-fold decreased risk of diffuse large B-cell lymphoma (OR 0.56, 95% CI 0.34–0.92, p = 0.02), the major subtype of NHL. Overall, our study identifies that XPD polymorphisms may be important in the aetiology of NHL although analysis of additional polymorphisms and extended haplotype studies are required to clarify their role.     

Contribution of flow cytometric immunophenotyping to the evaluation of tissues with suspected lymphoma?

BACKGROUND: A critical analysis of the contribution of flow cytometric immunophenotyping (FCI) to the evaluation of lymph nodes and extranodal tissues with suspected lymphoma by a large, retrospective approach has not been reported previously and represents the purpose of this study. METHODS: A total of 278 lymph nodes and 95 extranodal tissue specimens submitted over a 2-year period with complete histologic, FCI, and immunohistochemical (IH) data formed the basis of the study. RESULTS: The FCI data contributed significantly to or was consistent with the final tissue diagnosis in the majority (94%) of the tissue samples. There is no well-described utility of flow cytometry markers for Hodgkin's lymphoma (HL) due to the usual scarcity of tumor cells in the final cell suspensions obtained from these tumors. However, the FCI data excluded non-Hodgkin's lymphoma (NHL) and suggested the possible usefulness of CD15 and CD30 by FCI in HL. In addition, immunophenotypic data by FCI in combination with touch imprint cytomorphology was useful in excluding a diagnosis of NHL in cases of nonhematopoietic malignancies and was particularly useful in defining the following hematopoietic tumors and malignancies: thymoma, T-cell lymphoblastic lymphoma, leukemia cutis, and plasma cell dyscrasia. Thus, IH was not essential for the diagnosis in these latter cases and was performed in only two cases (one thymoma and one plasma cell dyscrasia). Of interest, FCI supported the diagnosis in 3 cases of Ewing's sarcoma/primitive neuroectodermal tumor by detection of CD56 on the surface of the malignant cell. Only 11% of NHL were "negative" by FCI (i.e., an aberrant T-cell or monoclonal B-cell population was not identified). Reasons for these discrepancies included partial tissue involvement by the NHL with sampling differences, T-cell rich or lymphohistiocytic-rich variants with a small population of monoclonal B cells, marked tumoral sclerosis, poor tumor preservation, and T-cell NHL without an aberrant immunophenotype. Only 60% of CD30+ anaplastic large cell lymphomas (ALCL) were CD30+ by FCI. CONCLUSIONS: FCI data should always be correlated with light microscopy if no FCI abnormalities are detected; IH may need to be performed in selected cases. It is less necessary to perform microscopic examination of tissues when the FCI data are positive and indisputable. However, in selected cases in which FCI data is diagnostic, microscopic observations may provide additional information due to sampling.     

CXCR5 polymorphisms in non-Hodgkin lymphoma risk and prognosis

CXCR5 [chemokine (C-X-C motif) receptor 5; also known as Burkitt lymphoma receptor 1 (BCR1)] is expressed on mature B-cells, subsets of CD4⁺ and CD8⁺ T-cells, and skin-derived migratory dendritic cells. Together with its ligand, CXCL13, CXCR5 is involved in guiding B-cells into the B-cell zones of secondary lymphoid organs as well as T-cell migration. This study evaluated the role of common germline genetic variation in CXCR5 in the risk and prognosis of non-Hodgkin lymphoma (NHL) using a clinic-based study of 1,521 controls and 2,694 NHL cases including 710 chronic lymphocytic leukemia/small lymphocytic lymphoma, 586 diffuse large B-cell lymphoma (DLBCL), 588 follicular lymphoma (FL), 137 mantle cell lymphoma (MCL), 230 marginal zone lymphoma (MZL), and 158 peripheral T-cell lymphoma (PTCL). Of the ten CXCR5 tag SNPs in our study, five were associated with risk of NHL, with rs1790192 having the strongest association (OR 1.19, 95 % CI 1.08–1.30; p = 0.0003). This SNP was most strongly associated with the risk of FL (OR 1.44, 95 % CI 1.25–1.66; p = 3.1 × 10^?7), with a lower degree of association with DLBCL (OR 1.16, 95 % CI 1.01–1.33; p = 0.04) and PTCL (OR 1.29, 95 % CI 1.02–1.64; p = 0.04) but no association with the risk of MCL or MZL. For FL patients that were observed as initial disease management, the number of minor alleles of rs1790192 was associated with better event-free survival (HR 0.64; 95 % CI 0.47–0.87; p = 0.004). These results provide additional evidence for a role of host genetic variation in CXCR5 in lymphomagenesis, particularly for FL.     

抗CD20单克隆抗体治疗B 细胞淋巴瘤的效应机制

B细胞淋巴瘤是一种主要的非霍奇金淋巴瘤(non-Hodgkin’s lymphoma,NHL),95%以上的B细胞淋巴瘤均表达B细胞分化抗原CD20。尽管目前CD20在B细胞分化发育过程中的具体功能尚未阐明,但其特有的表达方式和在细胞膜上的分布特点决定了其成为B细胞淋巴瘤靶向治疗的主要靶点。近十年来,随着抗CD20单克隆抗体的不断发展和进步,联合传统的CHOP化疗方案,在NHL的治疗中显示出良好的效果。虽然,近年来抗CD20单抗逐渐被用于B细胞相关的自身免疫病的治疗,但相关作用机制尚不明确。在针对NHL的临床治疗中,抗CD20单抗的疗效被认为依赖于效应器机制,主要有ADCC、CDC和细胞凋亡。虽然抗CD20在淋巴瘤的治疗中具有显著的免疫疗效,但部分瘤荷较大的病人出现了耐药和复发,循环中大量B细胞由于单抗的结合而被机体的单核巨噬细胞吞噬或NK细胞杀伤,机体出现成熟B细胞空缺期,同时单核巨噬细胞、NK细胞和补体大量消耗,造成机体免疫效应功能饱和和效应器耗竭。本文就抗CD20单克隆抗体在治疗淋巴瘤中的具体作用机制及可能造成的机体效应器耗竭问题做一简要的概述。     

Primary non-Hodgkin's lymphoma of the breast: a case report

Extranodal non-Hodgkin's lymphoma (NHL) of the breast is a rare entity. It represents 0.04-1.1% of malignant tumors of the breast. 1.7-2.2% of extranodal lymphomas and 0.7% of all NHL. However, primary NHL (PNHL) is the most frequent hematopojetic tumor of the breast. CASE: A 23-year-old woman presented with a mass in the left breast for 3 months followed by enlarged left axillary lymph nodes. Mammography showed a diffuse increase in the density of the left breast. Other investigations were unremarkable. Both fine needle aspiration cytology (FNAC) and histopathology were diagnostic of NHL. Immunohistochemistry was confirmatory of NHL, diffuse large cell type, of B-cell lineage. CONCLUSION: Primary and secondary lymphomas of the breast, though rare, should be considered in the differential diagnosis of breast malignancies. PNHL of the breast is usually right sided, but this patient had left breast involvement. Diagnosis by FNAC was successful as the cytologic picture is similar to that of any other lymphoid or extranodal NHL. When histopathology and immunohistopathology are conclusive, FNAC, supplemented by immunocytochemistry, can be applied as a simple, reliable and cost-effective tool in the early diagnosis of breast lymphomas.     

CHOP Chemotherapy for Aggressive Non-Hodgkin Lymphoma with and without HIV in the Antiretroviral Therapy Era in Malawi

There are no prospective studies of aggressive non-Hodgkin lymphoma (NHL) treated with CHOP in sub-Saharan Africa. We enrolled adults with aggressive NHL in Malawi between June 2013 and May 2015. Chemotherapy and supportive care were standardized, and HIV+ patients received antiretroviral therapy (ART). Thirty-seven of 58 patients (64%) were HIV+. Median age was 47 years (IQR 39–56), and 35 (60%) were male. Thirty-five patients (60%) had stage III/IV, 43 (74%) B symptoms, and 28 (48%) performance status ≥2. B-cell NHL predominated among HIV+ patients, and all T-cell NHL occurred among HIV- individuals. Thirty-one HIV+ patients (84%) were on ART for a median 9.9 months (IQR 1.1–31.7) before NHL diagnosis, median CD4 was 121 cells/μL (IQR 61–244), and 43% had suppressed HIV RNA. HIV+ patients received a similar number of CHOP cycles compared to HIV- patients, but more frequently developed grade 3/4 neutropenia (84% vs 31%, p = 0.001), resulting in modestly lower cyclophosphamide and doxorubicin doses with longer intervals between cycles. Twelve-month overall survival (OS) was 45% (95% CI 31–57%). T-cell NHL (HR 3.90, p = 0.017), hemoglobin (HR 0.82 per g/dL, p = 0.017), albumin (HR 0.57 per g/dL, p = 0.019), and IPI (HR 2.02 per unit, p<0.001) were associated with mortality. HIV was not associated with mortality, and findings were similar among patients with diffuse large B-cell lymphoma. Twenty-three deaths were from NHL (12 HIV+, 11 HIV-), and 12 from CHOP (9 HIV+, 3 HIV-). CHOP can be safe, effective, and feasible for aggressive NHL in Malawi with and without HIV.     

Lymphoma subtype incidence rates in children and adolescents: first report from Brazil

BackgroundLymphoma is the third most common pediatric malignancy. The purpose of this study was to analyze the incidence rates of lymphoma in children and adolescents in Brazil.MethodsAll cases of Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and Burkitt lymphoma (BL) were extracted from 14 population-based cancer registries (PBCRs) from 2000 to 2005, and included children and adolescents 0–19 years old. Analyses included age-adjusted incidence rates (AAIRs) and age-specific incidence rates (ASIRs) by each PBCR. A social exclusion index (SEI) was built and used as proxy for socioeconomic status (SES) levels. Correlations between SES and incidence rates were investigated using Spearman's test.ResultsThe median incidence of lymphoma was 22.7/million. AAIRs of lymphomas varied from 12.9 (Salvador) to 34.5 per million (São Paulo). Median AAIR was 8.8/million, 9.8/million, and 2.9/million for NHL, HL, and BL, respectively. In all PBCRs except that of Recife, AAIR was slightly higher in males than females. The median ASIR was highest for HL (18.5/million) at 15–19 years for both genders. For NHL there were two peaks for ASIR: 11.1/million (1–4 years of age) and 13.2/million (15–19 years of age). The median ASIR for BL was highest among children aged 1–4 years (4.7/million) and in males. Higher SEI correlated with higher incidence of HL (P = 0.06), whereas rates of NHL and BL did not correlate with SEI. Borderline different incidence rates were observed in HL correlated with cities with higher SEIs.ConclusionIncidence rates of lymphomas in Brazil do not differ compared to rates reported worldwide, although SES differences deserve further investigation.     

Age, sex, race, initial fitness, and response to training: the HERITAGE Family Study.

Effects of age, sex, race, and initial fitness on training responses of maximal O(2) uptake (VO(2 max)) are unclear. Data were available on 435 whites and 198 blacks (287 men and 346 women), aged 17-65 yr, before and after standardized cycle ergometer training. Individual responses varied widely, but VO(2 max) increased significantly for all groups. Responses by men and women and by blacks and whites of all ages varied widely. There was no sex difference for change (Delta) in VO(2 max) (ml. kg(-1). min(-1)); women had lower initial values and greater relative (%) increases. Blacks began with lower values but had similar responses. Older subjects had a lower Delta but a similar percent change. Baseline VO(2 max) correlated nonsignificantly with DeltaVO(2 max) but significantly with percent change. There were high, medium, and low responders in all age groups, both sexes, both races, and all levels of initial fitness. Age, sex, race, and initial fitness have little influence on VO(2 max) response to standardized training in a large heterogeneous sample of sedentary black and white men and women.     

Renal Involvement in Non-Hodgkin Lymphoma: Proven by Renal Biopsy

Aims

To determine the spectrum of renal lesions in patients with kidney involvement in non-Hodgkin''s lymphoma (NHL) by renal biopsy.

Methods

The clinical features and histological findings at the time of the renal biopsy were assessed for each patient.

Results

We identified 20 patients with NHL and renal involvement, and the diagnosis of NHL was established following the kidney biopsy in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n = 4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T-cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had impaired renal function. The pathological findings included (1) membranoproliferative glomerulonephritis-like pattern in seven patients; (2) crescent glomerulonephritis in four; (3) minimal-change disease in three, and glomeruli without specific pathological abnormalities in three; (4) intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one; and (7) lymphoma infiltration of the kidney in eight patients.

Conclusion

A wide spectrum of renal lesions can be observed in patients with NHL, and NHL may be first proven by renal biopsies for evaluation of kidney injury or proteinuria. Renal biopsy is necessary to establish the underlying cause of renal involvement in NHL.     

Long non-coding RNA as a novel biomarker and therapeutic target in aggressive B-cell non-Hodgkin lymphoma: A systematic review

Cancer initiation and progression have been associated with dysregulated long non-coding RNA (lncRNA) expression. However, the lncRNA expression profile in aggressive B-cell non-Hodgkin lymphoma (NHL) has not been comprehensively characterized. This systematic review aims to evaluate the role of lncRNAs as a biomarker to investigate their future potential in the diagnosis, real-time measurement of response to therapy and prognosis in aggressive B-cell NHL. We searched PubMed, Web of Science, Embase and Scopus databases using the keywords “long non-coding RNA”, “Diffuse large B-cell lymphoma”, “Burkitt's lymphoma” and “Mantle cell lymphoma”. We included studies on human subjects that measured the level of lncRNAs in samples from patients with aggressive B-cell NHL. We screened 608 papers, and 51 papers were included. The most studied aggressive B-cell NHL was diffuse large B-cell lymphoma (DLBCL). At least 79 lncRNAs were involved in the pathogenesis of aggressive B-cell NHL. Targeting lncRNAs could affect cell proliferation, viability, apoptosis, migration and invasion in aggressive B-cell NHL cell lines. Dysregulation of lncRNAs had prognostic (e.g. overall survival) and diagnostic values in patients with DLBCL, Burkitt's lymphoma (BL), or mantle cell lymphoma (MCL). Furthermore, dysregulation of lncRNAs was associated with response to treatments, such as CHOP-like chemotherapy regimens, in these patients. LncRNAs could be promising biomarkers for the diagnosis, prognosis and response to therapy in patients with aggressive B-cell NHL. Additionally, lncRNAs could be potential therapeutic targets for patients with aggressive B-cell NHL like DLBCL, MCL or BL.     

Genetic polymorphisms in the oxidative stress pathway and susceptibility to non-Hodgkin lymphoma

Oxidative damage caused by reactive oxygen species (ROS) and other free radicals is involved in a number of pathological conditions including cancer. In a population-based case-control study of non-Hodgkin lymphoma (NHL) (n = 518 cases, 597 controls) among women in Connecticut, we analyzed one or more single nucleotide polymorphisms (SNPs) in ten candidate genes (AKR1A1, AKR1C1, AKR1C3, CYBA, GPX1, MPO, NOS2A, NOS3, OGG1, and SOD2) that mediate oxidative stress directly or indirectly in the NADPH oxidase-dependent respiratory burst. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and race. Polymorphisms in AKR1A1 and CYBA were significantly associated with increased risk of NHL. There was a 1.7-fold (95% CI = 1.2–2.4, P = 0.0047) increased risk of NHL for individuals who were variant homozygous for the AKR1A1 (IVS5 + 282T > C) SNP. The effect was most pronounced for risk of diffuse large B-cell lymphoma, but risk estimates were non-significantly elevated for other common B-cell histologies and T-cell lymphomas as well. In addition, individuals variant homozygous for the CYBA (Ex4 + 11C > T) SNP had a 1.6-fold (95% CI = 1.1–2.4, P = 0.019) increased risk of NHL that was particularly pronounced for T-cell lymphoma (OR = 3.5, 95% CI = 1.3–9.6, P = 0.013), but was also associated with non-significant increased risks for each of the common B-cell histologies. These results suggest that SNPs in genes related to the oxidative stress pathway may be associated with increased risk of NHL. Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users. The US Government’s right to retain a non-exclusive, royalty-free license in and to any copyright is acknowledged.     

Overexpression of microRNAs from the miR-17-92 paralog clusters in AIDS-related non-Hodgkin's lymphomas

Background

Individuals infected by HIV are at an increased risk for developing non-Hodgkin''s lymphomas (AIDS-NHL). In the highly active antiretroviral therapy (HAART) era, there has been a significant decline in the incidence of AIDS-associated primary central nervous system lymphoma (PCNSL). However, only a modest decrease in incidence has been reported for other AIDS-NHL subtypes. Thus, AIDS-NHLs remain a significant cause of morbidity and mortality in HIV infected individuals. Recently, much attention has been directed toward the role of miRNAs in cancer, including NHL. Several miRNAs, including those encoded by the miR-17-92 polycistron, have been shown to play significant roles in B cell tumorigenesis. However, the role of miRNAs in NHL in the setting of HIV infection has not been defined.

Methodology/Principal Findings

We used quantitative realtime PCR to assess the expression of miRNAs from three different paralog clusters, miR-17-92, miR-106a-363, and miR-106b-25 in 24 cases of AIDS-NHLs representing four tumor types, Burkitt''s lymphoma (BL, n = 6), diffuse large B-cell lymphoma (DLBCL, n = 8), primary central nervous system lymphoma (PCNSL, n = 5), and primary effusion lymphoma (PEL, n = 5). We also used microarray analysis to identify a differentiation specific miRNA signature of naïve, germinal center, and memory B cell subsets from tonsils (n = 4). miRNAs from the miR-17-92 paralog clusters were upregulated by B cells, specifically during the GC differentiation stage. We also found overexpression of these miRNA clusters in all four AIDS-NHL subtypes. Finally, we also show that select miRNAs from these clusters (miR-17, miR-106a, and miR-106b) inhibited p21 in AIDS-BL and DLBCL cases, thus providing a mechanistic role for these miRNAs in AIDS-NHL pathogenesis.

Conclusion

Dysregulation of miR-17-92 paralog clusters is a common feature of AIDS-associated NHLs.     

Incidence,mortality and receptor status of breast cancer in African Caribbean women: Data from the cancer registry of Guadeloupe

BackgroundGeographical disparities in breast cancer incidence and outcomes are reported worldwide. Women of African descent show lower incidence, higher mortality rates and earlier age of onset. We analyzed data from the cancer registry of Guadeloupe for the period 2008–2013.MethodsWe describe breast cancer characteristics by molecular subtype, as well as estimated observed and net survival. We used Cox proportional hazard models to determine associations between cancer subtypes and death rate, adjusted for variables of interest.ResultsOverall, 1275 cases were recorded with a mean age at diagnosis of 57(±14) years. World standardized incidence and mortality were respectively 71.9/100,000 and 14.1/100,000 person-years. Age-specific incidence rates were comparable to European and US populations below the age of 45, and higher in Guadeloupean women aged between 45 and 55 years. Overall, 65.1% of patients were hormone receptor (HR)+ and 20.1% were HR-. Triple negative breast cancers (TNBC) accounted for 14% of all cases, and were more frequent in patients under 40 (21.6% vs. 13.4%, p = 0.02). Five-year net survival was 84.9% [81.4-88.6]. It was higher for HR+/Her2+ and HR+/Her2- subtypes, and lower for HR-/Her2+ and TNBC patients.ConclusionWe found high age-specific incidence rates of breast cancer in women aged 45 to 55 years, which warrants further investigation in our population. However, this population of mainly African descent had good overall survival rates, and data according to subtypes are consistent with those reported internationally. These results may suggest that poorer survival in other African descent populations may not be an inherent feature of the disease but may be amenable to improvement.     

Apoptotic index from fine needle aspiration cytology as a criterion to predict histologic grade of non-Hodgkin's lymphoma

OBJECTIVE: To investigate whether the assessment of apoptotic index (AI) from fine needle aspiration (FNA) smears of non-Hodgkin's lymphomas (NHL) is reliable and has potential utility as a criterion to predict histologic grade. STUDY DESIGN: AI was independently determined by four cytopathologists as a percentage from routine FNA smears in 96 NHLs and 15 lymphoid hyperplasias. Working formulation (WF) grades from corresponding surgical biopsies were modified to include mantle zone-derived NHLs as intermediate grade and to make diffuse large cell NHL a separate category called "high" grade, whereas WF high grade NHLs were called "very high" grade. Histologic grades were also derived from the Revised European American Lymphoma (REAL) classification. AI was compared with histologic grade using the unpaired, two-tailed Student t test. These data were used to determine potential thresholds for AI that separate lower from higher grade NHLs. RESULTS: Measurements of AI strongly correlated between cytopathologists (median r = .93). Low and intermediate grade NHLs had indistinguishable AIs, whereas higher grade NHLs had significantly higher AIs. Appropriate potential AI thresholds between low or intermediate grade and higher grade NHLs were in the range of 1.5-2.5% (modified WF) and 1-2% (REAL). CONCLUSION: There is excellent interobserver reliability in the measurement of AI from FNAs of NHLs. Higher AIs distinguish higher from lower grade NHLs. Diffuse large cell NHLs had AIs that were similar to WF high grade NHLs.